Tid: 10 oktober 2011 kl 15.15-16.00.

Föredragshållare: Frank Miller, AstraZeneca, Södertälje

Titel: Blinded continuous monitoring of the nuisance parameter in clinical trials

Abstract: Determination of a clinical trial's size is an important task in the planning of any trial because of the direct implications of the sample size on feasibility, costs and timelines. However, sample size calculations are often subject to substantial uncertainty due to limited prior information on the size of nuisance parameters such as variances or event rates. Continuous monitoring of the nuisance parameter in clinical trials has been proposed as a tool to size trials appropriately. With this approach, the nuisance parameter is continuously monitored during the trial. The trial is stopped when the actual estimate for the nuisance parameter and sample size fulfill a stopping criterion. Continuous monitoring can therefore be viewed as stochastic process with stopping time.

In this presentation we describe the bias that occurs in unblinded continuous monitoring of the variance by means of a simulation study. Then we propose a procedure for blinded continuous monitoring that would not require breaking the treatment code during the ongoing study and show that the procedure does not suffer from the same biases observed in unblinded monitoring. Results on the performance properties of such designs are given and the designs are compared to blinded reestimation procedures with a single data look. Furthermore, we present a hypertension trial where blinded sample size reestimation with a single data look was applied and investigate the properties of blinded continuous monitoring in this setting. Finally we close with a brief discussion. This is joint work with Tim Friede, Dept. of Medical Statistics, University Medical Center Göttingen, Germany.

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